PB88-243191
HAZARD EVALUATION DIVISION
STANDARD EVALUATION PROCEDURE
PRODUCT CHEMISTRY
Prepared by
Randolph B. Perfetti, Ph.D.
Standard Evaluation Procedures Project Manager
Stephen L. Johnson
Hazard Evaluation Division
Office of Pesticide Programs
United States Environmental Protection Agency
Office of Pesticide Programs
Washington, D.C. 20460
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IS. Abstract (Limit 200 verds)
Detailed, stepwise procedures for the evaluation of -
product chemistry data are provided. Topics on Product
Identity and Composition (Guideline Reference Numbers 61-1,2,3 ,),
Analysis and Certification of Product Ingredients (Reference “•
Numbers 62—1,2,3), Physical and Chemical Characteristics
(Reference Numbers 63-2 thru 63-2 1) and Other Requirements
(Reference Number 64-1) are explained and important informati4
to be discussed is identified. Special emphasis is placed on the
evaluation of Topics 61—1,2,3 and 62—1,2,3 to assure that the
occurance of any especially toxic impurities in a product are
examined in detail.
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STANDARD EVALUATION PROCEDURE
PREAMBLE
This Standard Evaluation Procedure (SEP) is one of a set
of guidance documents which explain the procedures used to
evaluate environmental and human health effects data submitted
to the Office of Pesticide Programs. The SEPs are designed
to ensure comprehensive and consistent treatment of major
scientific topics in these reviews and to provide interpretive
policy guidance where appropriate. The Standard Evaluation
Procedures will be used in conjunction with the appropriate
Pesticide Assessment Guidelines and other Agency Guidelines.
While the documents were developed to explain specifically
the principles of scientific evaluation within the Office of
Pesticide Programs, they may also be used by other offices in
the Agency in the evaluation of studies and scientific data.
The Standard Evaluation Procedures will also serve as valuable
internal reference documents and will inform the public and
regulated community of important considerations in the
evaluation of test data for determining chemical hazards. I
believe the SEPs will improve both the quality of science
within EPA and, in conjunction with the Pesticide Assessment
Guidelines, will lead to more effective use of both public
and private resources.
Anne L. Barton, Acting Director
Hazard Evaluation Division
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TABLE OF CONTENTS
Page
I • INTRODUCTION . • . . . . . . . . . • . . . . . . . . . 1
A. Purpose of the Standard Evaluation Procedure . . . 1
B. Background Information • . . . . . . . . . . . . . 1
C. Objective of Product Chemistry . . . . . . . . . • 1
II. INFORMATIONTOBESUPPLIED . . . .. • . . . . . . . .1
III. THE DATA EVALUATIONPROCESS . . . . . . . . . . . . . .1
A. Prepare a Topical Discussion . • . . . . . . . . . 1
1. Product Identity • . . . . . . . . . • . . . . 3
2. Analysis and Certification of Product
Ingredients . . . . . . • . • . . . . • . . 3
3. Physical and Chemical Characteristics • . . . 4
4. Other Requirements . • . . . . • • . • . • . . 4
B. Identify Data Gaps . . . . . • . . • • . . . . . . 4
C. Interactions with Other RED Branches . . . . . . . 4
IV. APPENDICES . . • . . • . . . . . . . . . . . . . • • • 6
Appendix 1: Major Points to Consider in
Evaluating Product Chemistry . . . . . . 6
Appendix 2: Reviewer Aids Materials . . . . . . . • . 8
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PRODUCT CHEMISTRY
I. INTRODUCTION
A. Purpose of the Standard Evaluation procedure
This procedure is designed to aid Residue Chemistry
Branch (RCB) reviewers in their evaluations of studies submitted
by manufacturers/registrants/petitioners on the chemistry of
their products.
B. Background Information
A product chemistry profile of a pesticide product is
required under “Data Requirements for Pesticide Registration;
Final Rule” (49 FR (207) 42890, October 24, 1984) (40 CFR
158.190) to support its registration or reregistration.
Certain product chemistry information is also required
when petitions for tolerances for pesticides are submitted for
review. These data should be contained in Section A of the
petition.
C. Objective of Product Chemistry
Product chemistry data should answer the question:
What is the chemical nature of the pesticide product for which
registration or establishment of tolerances is being considered?
II. INFORMATION TO BE SUPPLIED
The manufacturer’s/registrant’s/petitioner’s reports should
include all information necessary to provide complete and
accurate topical discussions of the pesticide product; the
identity of its active ingredient, impurities and intentionally
added ingredients, how it is manufactured, how it may be detected
or measured, and how it should be handled and packaged. The
latter two requirements do not necessarily pertain to petitions
for tolerances.
Pesticide Assessment Guidelines Subdivision D — Product
Chemistry — provides guidance for this purpose.
III. THE DATA EVALUATION PROCESS
A. Prepare a Topical Discussion
The reviewer carefully examines and discusses each type
of information/data submitted by the manufacturer/registrant/
petitioner. Corresponding to each category of the discussions
listed below is the Guidelines Reference Number (See “Data
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Requirements for Pesticide Registration; Final Rule, 49 FR (207)
42890, October 24, 1984, which is incorporated herein by this
reference) for each of the types of data required under 40 CFR
Part 158. These data illustrate the minimum data that the Agency
usually requires to adequately assess the chemical characteristics
of a pesticide with respect to Registration Standards.
Guidelines
Categpry of Data Reference Number
Product Identity 61 — 1,2,3
Analysis and Certification of
Product Ingredients 62 — 1,2,3
Physical and Chemical
Characteristics 63—2 thru 63—21
Other Requirements 64—1
If there is more than one producer of a certain chemical,
a complete data set is required for each of the technical
products. Exceptions to this would be those physical properties
where the material tested would be the purified active ingredient
(PAl), i.e., the octanol/water partition coefficient, solubility,
vapor pressure, and dissociation constant. The requirement for a
complete data set from each producer of a technical chemical
would not ordinarily be encountered in a pesticide petition
review where only one producer petitions for a tolerance for his
technical product.
The following materials may be used to generate product
chemistry data: The PAl which is an analytical reference
standard chemical; the technical grade active ingredient (TGAI)
which is the chemical as it is manufactured before the addition of
any inert ingredients; and the manufacturing—use product (MP)
which can be the TGAI or the TGAI with inert ingredients added to
facilitate the subsequent formulation of the material into the end—
use product (EP) which is the chemical in the form in which it is
used as a pesticide.
At present, RCB reviews the complete product chemistry
data set for the technical product. Data reviewed by RCB for MPs
do not include the physical/chemical properties of the MP.
With respect to the product chemistry requirements, it
is important to determine that the proper test chemical, i.e.,
PAl, TGAI, MP, or EP, is employed for each topical requirement in
the Product Chemistry Guidelines. This is especially critical
with respect to the physical/chemical properties.
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Data requirements for pesticide petitions generally
include chemical identity, manufacturing process, impurities
found in the product and inerts added to the product. A
determination of whether added inerts in the product are cleared
under appropriate sections of 40 CFR 180.1001 is also required
for pesticide petitions (Sections A and/or B).
1. Product Identity (61—1, 61—2, 61—3 )
- A definition of the pesticide’s chemical identity
is necessary as the starting point in any review for three
reasons: a) to locate relevant scientific literature sources; (b)
to determine which pesticide products fall under the regulatory
authorities of the Agency; and c) to identify the essential
ingredients to be studied in the evaluation of pesticide hazards.
In general, a chemical’s identity is defined by
names, numbers, and symbols. This can include common names,
chemical names, representative trade names, names of manufacturers,
molecular formulas and structures, CAS Numbers, Pesticide Chemical
Code (Shaughnessy) Numbers, or other alpha/numeric codes.
Beyond this, the identity of the pesticide chemical
may need qualification in additional ways. It may include
stereoisomers, related compounds, or various complex molecules of
indeterminate structure occurring in a mixture. It may also
include several derivatives of the pesticide chemical which are
known to have similar behavior and effect, as in the case of
salts and esters of an acid. An up—to—date description of the
manufacturing process of the pesticide chemical and its
formulated products is required to probe chemical or biological
differences which may be attributable to their manufacture. This
description is considered to be Confidential Business Information
(CBI), and must be protected. For this reason it is summarized
in a confidential appendix.
Information is required on the presence of
impurities or contaminants that may result from: a) chemical
reactions employed in the synthesis and purification of the
active ingredients; b) chemical reactions between the ingredients
used in the formulated products; c) chemical reactions between
the pesticide ingredients and chemicals that may leach from
packing materials; and d) changes in composition of formulated
products during storage.
2. Analysis and Certification of Product Ingredients
( 62—1, 62—2, 62—3 )
The submission of analytical methods for the
determination of the active ingredients, impurities, and
contaminants has a dual purpose: to ascertain that the
concentration of active ingredients, impurities, or contaminants
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claimed in the labels of any one of the formulated products is
correct, and to be used as a regulatory tool in the implementation
of enforcement programs carried out by EPA or any other regulatory
Agency. The methodology must comply with the Agency’s requirements
as stated in Part 158 of the CFR and in Guidance Information
available from the Agency on individual pesticide chemicals.
This information is not generally required in
Section A of a pesticide petition.
3. Physical and Chemical Characteristics (63—2 thru
63—21 )
The physical and chemical characteristics of the
pesticide chemical are addressed when these are pertinent to:
a) the behavior and fate of the pesticide chemical under normal
environmental conditions; b) the disclosure of direct/indirect
hazard potential during storage, transport, mixing, dilution,
and use of the pesticide chemical; and c) reliability of the
pesticide chemical used as the experimental source in studies
supporting registration submissions other than the one under
review. The required characteristics are listed in Part 158 of
the CFR.
This information is not generally required in
Section A of a pesticide petition.
4. Other Requirements (64—1 )
If the Agency requires it, an applicant must submit
a sample of the TGAI, the PA!, or formulated product conforming
to the limits certified under 62—2.
B. Identify Data Gaps
Using the available guidance, the reviewer looks for
data gaps — omissions in the information/data base submitted by
the manufacturer/registrant/petitioner in his reports. When
applicable and needed for better understanding of the product
chemistry, omissions in the information/data are discussed and
tabulated. When so identified, they are brought to the attention
of the Product Manager/RD and of the znanufacturer/registrant/
petitioner for corrective action.
If omissions exist in the data submitted, the reviewer
must defer judgment until corrective action has been made.
C. Interactions with Other RED Branches
In considering the appropriateness and adequacy of the
information/data submitted on product chemistry, the reviewer
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must consult with other HED branch(es) on matters which are
germane to reaching that decision.
Specific consultations must be made with Toxicology
Branch to obtain its opinion on the toxicological significance of
the impurities vis—a-vis that of the product originally used in
toxicological tests.
Specific referral(s) must be made to the Exposure
Assessment Branch to enable it to arrive at its own conclusions
regarding the environmental impact of the pesticide product.
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APPENDIX 1
MAIOR POINTS TO CONSIDER IN EVALUATING PRODUCT CHEMISTRY
Include the following:
A. Test Compound(s )
— What is the TGAI, and/or MP, and its purity?
— What is the EP(s) and how much of the active ingredient
does it contain?
— Does the EP(s) contain any other active ingredient(s)?
— What are the inert ingredients, and are they covered
by 40 CFR 180.1001(c) through Ce)?
— What is the EPA Registration Number if registered with
the Agency?*
— Who produces the active ingredient and where?
— Are there active isomers or related components of the
primary active ingredient?
— Is there more than one producer of the chemical? If
so, is there a complete data set for each of the
technical products?
— Is a complete Product Chemistry data set available
for TGAIs and/or MPs?
— Is the proper test chemical being employed for each
topical requirement of the Product Chemistry
guidelines?
B. Manufacturing Process(es )
— Is the manufacturing process currently in use and
adequately described?
— What are the impurities in the starting (beginning)
materials?*
— Are the impurities in the starting (beginning)
materials likely to contribute to the formation of
toxic ingredients?*
— Are deleterious solvents carried over into the
product?
— If the active ingredient is produced commercially by
two (or more) manufacturing processes, how do the
products differ one from the other in their intpurities?*
— Is the manufacturing process itself likely to produce
toxic ingredients?
— Is all CBI placed in confidential appendices for
limited circulation within the Agency?
*This information is not generally addressed in Section A of a
pesticide petition.
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C. Certified Limits*
— Has the registrant given routine compositional data
and certified his limits?
D. Analytical Methodology*
— Is there a convenient validated method(s) of
adequate sensitivity for the active ingredient,
impurities and intentionally added ingredients of
toxicological concern, in the TGAI, the MP, or EP
which is suitable for enforcing their certified
limits?
E. Physical/Chemical Properties*
— Are hazards expected from the use or transport of the
TGAI, MP, or EP of the active ingredient?
— Is degradation or reaction during storage apt to
produce toxic ingredients?
Note (1): Certain ingredients which are generally recognized to
be toxic, and which may be anticipated by chemists to be present
in the product include (but are not limited to) nitrosamthes,
dioxins, hexachlorobenzene, and ethylene thiourea.
Note (2): Some physical and chemical properties are not applicable
to a given product on the basis of its known chemistry.
*Thjs information is not generally required in Section A of a
pesticide petition.
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APPENDIX 2
REVIEWER AIDS MATERIALS
1. Code of Federal Regulations (40 CFR Part 158) General
Services Administration, Washington, DC, updated annually.
2. Subdivision D (Product Chemistry) of the Pesticide
Assessment Guidelines, prepared by OPTS/EPA, Washington,
DC (1982).
3. Acceptable Common Names and Chemical Names for the
Ingredient Statement on Pesticide Labels , 4th ed., C.R.
Bla].ock, et al., editors, OPP7 PA (1979) available from
National Technical Information Service, Springfield, VA.
4. Farm Chemicals Handbook , Meister Publishing Company,
Willoughby, OH, updated annually.
5. Nanogen Index: A Dictionary of Pesticide and Chemical
Pollutants, K. Packer, editor, Nanogens International,
Freedom, CA, 1975 (updated periodically by supplements) .
6. The Pesticide Manual , 7th ed., C.R. Worthing, editor,
The British Crop Protection Council, Lavenham Press
Limited, Suffolk, England (1983).
7. The Merck Index , 10th ed., M. Windholz, editor, Merck &
Company, Inc., Rahway, NJ (1983).
8. Pesticides Manufacturing and Toxic Materials Control
Encyclopedia , M. Sittig, Noyes Data Corporation, Park
Ridge, NJ (1980).
9. Official Methods of Anal3(sis of the Association of
Official Analytical Chemists , lOth—l4th eds., W.
Horwitz, editor, Association of Official Analytical
Chemists, Arlington, VA.
10. Environmental Protection Ag ency Manual of Chemical
Methods for Pesticides and Devices . W.R. Bontoyan, ed.,
U.S. Environmental Protection Agency. Published and
distributed by the Association of Official Analytical
Chemists, Arlington, VA (1976).
11. CIPAC Handbook , Vol. 1 (1970) and Vol. 1A (1980)
Collaborative Handbook. International Pesticides
Analytical Council Limited, Plant Pathology Laboratory,
Batching Green, Harpenden, liertfordshire, England.
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12. Analytical Methods for Pesticides and Plant Growth
Regulators . G. Zweig, and 1. Sherma, eds. Continuing
Series. Academic Press, New York, NY (1963—1978).
13. Dangerous Properties of Industrial Materials , 6th ed.,
N.I. Sax, Van Nostrand Reinhold Company, New York
(1984).
14. American Society for Testing and Materials. Annual Book
of ASTM Standards . Continuing Series. American Society
for Testing and Materials, 1916 Race Street, Philadelphia,
PA 19103.
15. Guidelines for Testing Chemicals , Organization for
Economic Cooperation and Development, 1750 Pennsylvania
Avenue NW., Washington, DC.
16. Toxic Substances Control — Discussion of premanufacture
testing policy and tec1ii ica1 issues; Request for comment,
Environmental Protection Agency, FEDERAL REGISTER 44 (53)
16240—16292 (March 16, 1979).
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